Search Results

Overview

Uniprot IDP09622
Protein NameDihydrolipoyl dehydrogenase, mitochondrial
Gene NameDLD
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
104 YYHMAHGKDFASRGI
122 EVRLNLDKMMEQKST
127 LDKMMEQKSTAVKAL
132 EQKSTAVKALTGGIA
143 GGIAHLFKQNKVVHV
146 AHLFKQNKVVHVNGY
155 VHVNGYGKITGKNQV
159 GYGKITGKNQVTATK
166 KNQVTATKADGGTQV
267 NFQRILQKQGFKFKL
277 FKFKLNTKVTGATKK
320 IGRRPFTKNLGLEEL
410 GKSEEQLKEEGIEYK
417 KEEGIEYKVGKFPFA
430 FAANSRAKTNADTDG
445 MVKILGQKSTDRVLG
66 KAAQLGFKTVCIEKN

Function

Lipoamide dehydrogenase is a component of the glycine cleavage system as well as an E3 component of three alpha-ketoacid dehydrogenase complexes (pyruvate-, alpha-ketoglutarate-, and branched-chain amino acid-dehydrogenase complex) (PubMed:15712224, PubMed:16442803, PubMed:16770810, PubMed:17404228, PubMed:20160912, PubMed:20385101). The 2-oxoglutarate dehydrogenase complex is mainly active in the mitochondrion (PubMed:29211711). A fraction of the 2-oxoglutarate dehydrogenase complex also localizes in the nucleus and is required for lysine succinylation of histones: associates with KAT2A on chromatin and provides succinyl-CoA to histone succinyltransferase KAT2A (PubMed:29211711). In monomeric form may have additional moonlighting function as serine protease (PubMed:17404228). Involved in the hyperactivation of spermatazoa during capacitation and in the spermatazoal acrosome reaction (By similarity). The pyruvate dehydrogenase (PDH) complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links cytoplasmic glycolysis and the mitochondrial tricarboxylic acid (TCA) cycle (Probable). It contains multiple copies of three enzymatic components: pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (E2) and dihydrolipoamide dehydrogenase (E3) (Probable). The E3 subunit catalyzes reoxidation of the dihydrolipoyl moiety on lipoyl-bearing domains (LBDs) of E2 with NAD+ as the ultimate electron acceptor (PubMed:16442803, PubMed:16770810, PubMed:20160912, PubMed:20385101)

Protein Sequence

10 MQSWSRVYCS 20 LAKRGHFNRI 30 SHGLQGLSAV 40 PLRTYADQPI 50 DADVTVIGSG 60 PGGYVAAIKA 70 AQLGFKTVCI 80 EKNETLGGTC 90 LNVGCIPSKA 100 LLNNSHYYHM 110 AHGKDFASRG 120 IEMSEVRLNL 130 DKMMEQKSTA 140 VKALTGGIAH 150 LFKQNKVVHV 160 NGYGKITGKN 170 QVTATKADGG 180 TQVIDTKNIL 190 IATGSEVTPF 200 PGITIDEDTI 210 VSSTGALSLK 220 KVPEKMVVIG 230 AGVIGVELGS 240 VWQRLGADVT 250 AVEFLGHVGG 260 VGIDMEISKN 270 FQRILQKQGF 280 KFKLNTKVTG 290 ATKKSDGKID 300 VSIEAASGGK 310 AEVITCDVLL 320 VCIGRRPFTK 330 NLGLEELGIE 340 LDPRGRIPVN 350 TRFQTKIPNI 360 YAIGDVVAGP 370 MLAHKAEDEG 380 IICVEGMAGG 390 AVHIDYNCVP 400 SVIYTHPEVA 410 WVGKSEEQLK 420 EEGIEYKVGK 430 FPFAANSRAK 440 TNADTDGMVK 450 ILGQKSTDRV 460 LGAHILGPGA 470 GEMVNEAALA 480 LEYGASCEDI 490 ARVCHAHPTL 500 SEAFREANLA ASFGKSINF

Gene Ontology

Classification GO ID Description
Cellular Component GO:0043159 acrosomal matrix
Cellular Component GO:0160157 branched-chain alpha-ketoacid dehydrogenase complex
Cellular Component GO:0005759 mitochondrial matrix
Cellular Component GO:0005739 mitochondrion
Cellular Component GO:0031514 motile cilium
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0005634 nucleus
Cellular Component GO:0160167 oxoadipate dehydrogenase complex
Cellular Component GO:0045252 oxoglutarate dehydrogenase complex
Cellular Component GO:0045254 pyruvate dehydrogenase complex
Molecular Function GO:0004148 dihydrolipoyl dehydrogenase (NADH) activity
Molecular Function GO:0050660 flavin adenine dinucleotide binding
Biological Process GO:0120551 2-oxoglutarate decarboxylation to succinyl-CoA
Biological Process GO:0006103 2-oxoglutarate metabolic process
Biological Process GO:0120552 branched-chain alpha-keto acid decarboxylation to branched-chain acyl-CoA
Biological Process GO:0009083 branched-chain amino acid catabolic process
Biological Process GO:0019474 L-lysine catabolic process to acetyl-CoA
Biological Process GO:0006086 pyruvate decarboxylation to acetyl-CoA
Biological Process GO:0006099 tricarboxylic acid cycle

Reference

[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.

[2] Hong H, Chen X, Wang H, Gu X, Yuan Y et al.. Global profiling of protein lysine lactylation and potential target modified protein analysis in hepatocellular carcinoma.. Proteomics 23(9):e2200432. 2023 May. PMID: 36625413.

[3] Shi CM, Wang QC, Li XL, Yang YH, Tang XY et al.. Global Profiling of Protein Lactylation in Human Hippocampi.. Proteomics Clin Appl 19(2):e202400061. 2025 Mar. PMID: 39610256.

[4] He J, Lai T, Zhou Z, Yang H, Lei Z et al.. Multiomics profiling reveals the involvement of protein lactylation in nonhomologous end joining pathway conferring radioresistance in lung adenocarcinoma cell.. Sci Rep 15(1):24651. 2025 Jul 9. PMID: 40634431.

[5] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.